Concurrent or layered treatment with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred): A retrospective study of real-world clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5026-5026
Author(s):  
Neal D. Shore ◽  
A. Oliver Sartor ◽  
Cora N. Sternberg ◽  
Fred Saad ◽  
Bertrand F. Tombal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Descriptive Analysis ◽  
Randomized Study ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Kaplan Meier ◽  
Radium 223 ◽  
Phase Iii Study

5026 Background: In clinical practice, Ra-223 is often combined with Enza or Abi/pred. ERA 223 (NCT02043678) showed increased fracture risk with concurrent Ra-223+Abi/pred. We assessed real-world symptomatic skeletal events (SSEs) and overall survival (OS) of pts with mCRPC who received concurrent or layered Ra-223+Enza or Abi/pred. Methods: Patients with mCRPC treated with Ra-223 in US cancer clinics from 1/01/2013 to 6/30/2017 were identified from a Flatiron prostate cancer registry of electronic health records. Treatment initiation defined subgroups: concurrent (both started within 30 days) or layered (1 started ≥30 days after the other). Baseline (BL) was the first dose of Ra-223. Descriptive analysis was performed for BL characteristics, SSEs, and OS (Kaplan–Meier). Results: Of 625 pts treated with Ra-223, 48% received Ra-223+Enza or Abi/pred. Layered treatment was more common (73%) than concurrent (27%). BL characteristics and clinical outcomes were summarized [Table]. Conclusions: In a real-world setting, Ra-223+Enza or Abi/pred treatment was mainly layered. SSE rates with layered vs concurrent Ra-223+Abi/pred varied between subgroups; results must be treated cautiously given small pt numbers and a non-randomized study. The ongoing PEACE III trial is investigating concurrent Ra-223+Enza; a Phase III study (ESCALATE) exploring layered Ra-223+Enza is planned. [Table: see text]

Concurrent or layered treatment (Tx) with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred): A retrospective study of real-world clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 50-50
Author(s):  
Neal D. Shore ◽  
Oliver A. Sartor ◽  
Cora N. Sternberg ◽  
Fred Saad ◽  
Bertrand F. TOMBAL ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Descriptive Analysis ◽  
Randomized Study ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Kaplan Meier ◽  
Radium 223 ◽  
Phase Iii Study

50 Background: In clinical practice, Ra-223 is often combined with Enza or Abi/pred. ERA 223 (NCT02043678) showed increased fracture risk with concurrent Ra-223+Abi/pred. We assessed real-world symptomatic skeletal events (SSEs) and overall survival (OS) of pts with mCRPC who received concurrent or layered Ra-223+Enza or Abi/pred. Methods: Patients with mCRPC treated with Ra-223 in US cancer clinics from 1/01/2013 to 6/30/2017 were identified from a Flatiron prostate cancer registry of electronic health records. Tx initiation defined subgroups: concurrent (both started within 30 days) or layered (1 started ≥30 days after the other). Baseline (BL) was the first dose of Ra-223. Descriptive analysis was performed for BL characteristics, SSEs, and OS (Kaplan–Meier). Results: Of 625 pts treated with Ra-223, 48% received Ra-223+Enza or Abi/pred. Layered Tx was more common (73%) than concurrent (27%). BL characteristics and clinical outcomes were summarized [Table]. Conclusions: Ra-223+Enza or Abi/pred Tx was mainly layered. SSE rates with layered vs concurrent Ra-223+Abi/pred varied between subgroups; results must be treated cautiously given small pt numbers and a non-randomized study. The ongoing PEACE III trial is investigating concurrent Ra-223+Enza; a Phase III study (ESCALATE) exploring layered Ra-223+Enza is planned. Clinical trial information: NCT02043678. [Table: see text]

Clinical outcome with concurrent or layered treatment with radium-223 and abiraterone: A retrospective study of real-world experience with patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
Daniel J. George ◽  
Cora N. Sternberg ◽  
A. Oliver Sartor ◽  
Fred Saad ◽  
Bertrand F. TOMBAL ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Study ◽  
Clinical Outcomes ◽  
Real World ◽  
Descriptive Analysis ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Skeletal Related Events

253 Background: Limited data exist on Ra-223 use in combination with Abi in a real-world setting. This retrospective study evaluated clinical outcomes in pts with mCRPC who received concurrent or layered Ra-223 + Abi treatment. Methods: This study used the Flatiron prostate cancer registry of electronic health records of pts with mCRPC treated with Ra-223 in US cancer clinics between 1/01/2013 and 6/30/2017. Two sub-cohorts were defined: pts treated with Ra-223 + Abi in a concurrent (both started within 30 days) or layered fashion (one of the two started over 30 days later). Descriptive analysis was done for baseline (BL) characteristics (prior to start of Ra-223), prior therapies, and clinical outcomes including skeletal-related events (SREs) and overall survival (OS). Results: 625 pts were treated with Ra-223; 136 (21.8%) received Ra-223 + Abi. Most received layered therapy (n = 97, 71%); concurrent start was less common (n = 39, 29%) [Table]. Conclusions: Prior to the start of Ra-223 therapy, half of the pts had prior SREs; almost one-fifth had prior pathologic fractures. Pts treated with Ra-223 + Abi had also received prior chemo and/or enzalutamide. SRE occurrence seems higher for concurrent treatment, but results should be cautiously interpreted due to low concurrent cohort size. OS in both cohorts exceeded the OS in the Phase III ALSYMPCA study (14.9 mo).[Table: see text]

Treatment patterns and outcomes for metastatic castration-resistant prostate cancer (mCRPC) in a real-world setting: A retrospective study of greater than 2500 patients.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 256-256 ◽  
Author(s):  
Celestia S. Higano ◽  
Cora N. Sternberg ◽  
Fred Saad ◽  
Bertrand F. TOMBAL ◽  
Kurt Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Descriptive Analysis ◽  
Treatment Patterns ◽  
Cross Resistance ◽  
Combination Regimen ◽  
Castration Resistant Prostate Cancer ◽  
Kaplan Meier ◽  
Radium 223 ◽  
Third Line

256 Background: In the era of expanding therapeutic options for mCRPC, there is a growing need to develop an optimal treatment sequence. This real-world study evaluated treatment patterns and outcomes in mCRPC patients. Methods: This retrospective cohort study used the Flatiron prostate cancer core registry (Jan 2013 to Sep 2017) to assess real-world treatment patterns (lines of therapy and transitions to subsequent lines) and outcomes (overall survival, OS) in patients with mCRPC. Descriptive analysis was performed for treatment patterns, and the Kaplan–Meier method was used to analyze OS. Results: This study comprised 2559 patients with mCRPC who received up to three lines of therapy. 23% of patients did not receive a life-prolonging therapy after the initial diagnosis of mCRPC. In the first-line (1L) setting, abiraterone (Abi, 37%) was the most-prescribed therapy, followed by enzalutamide (Enza, 28%) and docetaxel (15%). In the second line (2L), combination therapies were frequent (17%), with rates similar to taxane-based chemotherapy (docetaxel or cabazitaxel). Enza was the most-common 2L therapy used after Abi, and vice versa. Radium-223 (Ra-223) was prescribed as 1L therapy in 5% and 2L therapy in 9% of patients, either as monotherapy or part of a combination regimen. When Ra-223 was used in the 1L setting, similar proportions of patients received subsequent therapy with Enza (14%), Abi (13%), or chemotherapy (11%). Ra-223 was commonly used in the third line (14%), but less frequently than chemotherapy (36%). After each line, ~50% of patients did not receive a subsequent life-prolonging agent. Overall, 66% of patients used bone health agents at any time (denosumab, 48%; zoledronic acid, 24%). The median OS from the diagnosis of mCRPC was 21 months. Conclusions: This real-world study shows that not all patients with mCRPC received a life-prolonging therapy. Among patients who received an anti-cancer therapy, approximately half did not receive a subsequent life-prolonging therapy. Abi and Enza were the most-common 1L therapies, and their back-to-back use was common despite reported cross-resistance and limited benefit.

Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA4-LBA4
Author(s):  
Michael J. Morris ◽  
Johann S. De Bono ◽  
Kim N. Chi ◽  
Karim Fizazi ◽  
Ken Herrmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Standard Of Care ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Secondary Endpoints ◽  
Phase Iii Study

LBA4 Background: Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains invariably fatal. Prostate-specific membrane antigen (PSMA) is highly expressed in mCRPC lesions. 177Lu-PSMA-617 is a targeted radioligand therapy that delivers ß-particle radiation to PSMA-expressing cells and surrounding microenvironment. Method: VISION was an international, randomized, open-label phase III study evaluating 177Lu-PSMA-617 in men with PSMA-positive mCRPC previously treated with next-generation androgen receptor signaling inhibition and 1–2 taxane regimens. PSMA positivity (threshold greater than liver) was determined by central review of 68Ga-PSMA-11 scans. Patients were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks x 6 cycles) plus standard of care (SOC) versus SOC alone. SOC was investigator determined but excluded cytotoxic chemotherapy and radium-223. The alternate primary endpoints were radiographic progression-free survival (rPFS) using PCWG3 criteria by independent central review (ICR) and overall survival (OS). Under the null hypothesis, median rPFS was assumed to be 4 months and OS 10 months for 177Lu-PSMA-617 + SOC for a hazard ratio (HR) of 1.00. Under the alternative hypothesis, median rPFS was assumed to be 6 months for a HR of 0.67 and median OS was assumed to be 13.7 months for a HR of 0.7306. Key secondary endpoints were objective response rate (ORR; RECIST v1.1), disease control rate (DCR), and time to first symptomatic skeletal event (SSE). Results: Between 4 June 2018 and 23 October 2019, 831 of 1179 screened patients were randomized 2:1 to receive 177Lu-PSMA-617 + SOC (n = 551) or SOC only (n = 280). Median study follow-up was 20.9 months at the data cut-off (27 January 2021). Treatment groups were balanced in terms of demographics and baseline characteristics. 177Lu-PSMA-617 + SOC significantly improved rPFS versus SOC alone (median rPFS, 8.7 vs 3.4 months; HR, 0.40 [99.2% CI: 0.29, 0.57]; p < 0.001, one-sided). The alternate primary endpoint of OS was also significantly improved versus SOC alone (median OS, 15.3 vs 11.3 months; HR, 0.62 [95% CI: 0.52, 0.74]; p < 0.001, one-sided). All key secondary endpoints were statistically significant between the treatment arms in favor of 177Lu-PSMA-617 + SOC, including ICR-determined ORR (29.8% vs 1.7%), ICR-determined DCR (89.0% vs 66.7%) and time to first SSE (median time, 11.5 vs 6.8 months; HR, 0.50). While a higher rate of high-grade treatment-emergent adverse events was observed with 177Lu-PSMA-617 (52.7% vs 38.0%), therapy was well tolerated. Conclusions: 177Lu-PSMA-617 plus SOC treatment is a well-tolerated regimen that improves rPFS and prolongs OS compared with SOC alone in men with advanced-stage PSMA-positive mCRPC, supporting its adoption as a standard of care. Clinical trial information: NCT03511664.

Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 51-51
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Alexander Watson ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Survival Times ◽  
Free Survival

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Silke Gillessen ◽  
Ananya Choudhury ◽  
Alejo Rodriguez-Vida ◽  
Franco Nole ◽  
Enrique Gallardo Diaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Analysis ◽  
Phase Iii ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Administration ◽  
Castration Resistant ◽  
Radium 223 ◽  
Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

Multi-institutional evaluation of the clinical outcomes and genomic correlates of African Americans with metastatic castration-sensitive prostate cancer (mCSPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 17-17
Author(s):  
Meredith MI Freeman ◽  
Ellen Jaeger ◽  
Jason Zhu ◽  
Audrey Phone ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Analysis ◽  
Clinical Outcomes ◽  
De Novo ◽  
High Volume ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Treatment Intensification ◽  
Radium 223 ◽  
Incidence And Mortality

17 Background: Prostate cancer incidence and mortality is higher in African American (AA) as compared with non-AA men. The outcomes of mCSPC have significantly improved through treatment intensification yet, AA representation in those studies was suboptimal. We aimed to report the clinical, treatment outcomes and genomic data of AA men with mCSPC. Methods: Retrospective analysis of consecutive AA men with mCSPC at six Academic Institutions. The primary objective was to report the baseline characteristics and treatment patterns of mCSPC AA patients. The secondary objectives included the germline and somatic data and the clinical outcomes including PSA response, progression-free survival and subsequent treatments. Results: A total of 71 patients, median age 63 years (range, 41-84) with 58% Gleason 8-10, initial PSA of 69.8 ng/mL (0.02-7650), 59% with de-novo and 55% with high-volume (CHAARTED criteria; 20% visceral) disease, were included in this analysis. Twenty-two patients (31%) were treated with androgen deprivation therapy (ADT; 67% prior to year 2017), while 24%, 45% and 3% received docetaxel (median 6 cycles), abiraterone acetate and enzalutamide, respectively. Two patients received triplet therapy with ADT/docetaxel plus abiraterone or enzalutamide. Undetectable PSA was achieved in 35% after a median of 8.9 months (1.8-22.3). Among patients with mCSPC who received radiation therapy to prostate (n = 8), 89% had low volume disease. At time of cut off, thirty-two patients developed CRPC and the estimated median time to CRPC was 2.9 years (95% CI, 1.6-4.2). Subsequent therapies (n = 29) included abiraterone acetate (41%), enzalutamide (24%), bicalutamide (10%), radium-223 (7%), chemotherapy (7%), sipuleucel-T (3%) and others (7%). Five patients (8%) had pathogenic germline alterations (n = 2 BRCA1; n = 1 HOXB13, PALB2 and PMS2). Additionally, the most common somatic alterations among tested patients (n = 27) included CDK12, SPOP, TMPRSS2-ERG fusion, and TP53, all in 11% frequency. Of note, n = 2 BRCA1 and n = 1 high MSI/TMB. Conclusions: In one of the largest reported cohorts to our knowledge, mCSPC AA presented with a high number of de-novo and high-volume disease and might harbor a different germline and somatic genomic profile. The outcomes were comparable to contemporary phase III trials with treatment intensification, yet 31% were treated with ADT. Despite the known limitations associated with retrospective analysis, these data support prior observations where AA might have better initial PSA responses to ADT-based strategies compared with Caucasians, requiring further validation.

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